Per Skaane

Comparison of Digital Mammography Alone and Digital Mammography Plus Tomosynthesis in a Population-based Screening Program

PURPOSE To assess cancer detection rates, false-positive rates before arbitration, positive predictive values for women recalled after arbitration, and the type of cancers detected with use of digital mammography alone and combined with tomosynthesis in a large prospective screening trial. MATERIALS AND METHODS A prospective, reader- and modality-balanced screening study of participants undergoing combined mammography plus tomosynthesis, the results of which were read independently by four different radiologists, is under way. The study was approved by a regional ethics committee, and all participants provided written informed consent. The authors performed a preplanned interim analysis of results from 12,631 examinations interpreted by using mammography alone and mammography plus tomosynthesis from November 22, 2010, to December 31, 2011. Analyses were based on marginal log-linear models for binary data, accounting for correlated interpretations and adjusting for reader-specific performance levels by using a two-sided significance level of .0294. RESULTS Detection rates, including those for invasive and in situ cancers, were 6.1 per 1000 examinations for mammography alone and 8.0 per 1000 examinations for mammography plus tomosynthesis (27% increase, adjusted for reader; P = .001). False-positive rates before arbitration were 61.1 per 1000 examinations with mammography alone and 53.1 per 1000 examinations with mammography plus tomosynthesis (15% decrease, adjusted for reader; P < .001). After arbitration, positive predictive values for recalled patients with cancers verified later were comparable (29.1% and 28.5%, respectively, with mammography alone and mammography plus tomosynthesis; P = .72). Twenty-five additional invasive cancers were detected with mammography plus tomosynthesis (40% increase, adjusted for reader; P < .001). The mean interpretation time was 45 seconds for mammography alone and 91 seconds for mammography plus tomosynthesis (P < .001). CONCLUSION The use of mammography plus tomosynthesis in a screening environment resulted in a significantly higher cancer detection rate and enabled the detection of more invasive cancers. Clinical trial registration no. NCT01248546.

Two-View Digital Breast Tomosynthesis Screening with Synthetically Reconstructed Projection Images: Comparison with Digital Breast Tomosynthesis with Full-Field Digital Mammographic Images

PURPOSE To compare the performance of two versions of reconstructed two-dimensional (2D) images in combination with digital breast tomosynthesis (DBT) versus the performance of standard full-field digital mammography (FFDM) plus DBT. MATERIALS AND METHODS This trial had ethical committee approval, and all participants gave written informed consent. Examinations (n = 24 901) in women between the ages of 50 and 69 years (mean age, 59.2 years) were interpreted prospectively as part of a screening trial that included independent interpretations of FFDM plus DBT and reconstructed 2D images plus DBT. Reconstructed 2D images do not require radiation exposure. Using analyses for binary data that accounted for correlated interpretations and were adjusted for reader-specific volume, two versions (initial and current) of reconstructed 2D images used during trial periods 1 (from November 22, 2010, to December 21, 2011; 12 631 women) and 2 (from January 20, 2012, to December 19, 2012; 12 270 women) were compared in terms of cancer detection and false-positive rates with the corresponding FFDM plus DBT interpretations. RESULTS Cancer detection rates were 8.0, 7.4, 7.8, and 7.7 per 1000 screening examinations for FFDM plus DBT in period 1, initial reconstructed 2D images plus DBT in period 1, FFDM plus DBT in period 2, and current reconstructed 2D images plus DBT in period 2, respectively. False-positive scores were 5.3%, 4.6%, 4.6%, and 4.5%, respectively. Corresponding reader-adjusted paired comparisons of false-positive scores revealed significant differences for period 1 (P = .012) but not for period 2 (ratio = 0.99; 95% confidence interval: 0.88, 1.11; P = .85). CONCLUSION The combination of current reconstructed 2D images and DBT performed comparably to FFDM plus DBT and is adequate for routine clinical use when interpreting screening mammograms.

Studies Comparing Screen-Film Mammography and Full-Field Digital Mammography in Breast Cancer Screening: Updated Review

Full-field digital mammography (FFDM) has several potential benefits as compared with screen-film mammography (SFM) in mammography screening. Digital technology also opens for implementation of advanced applications, including computer-aided detection (CAD) and tomosynthesis. Phantom studies and experimental clinical studies have shown that FFDM is equal or slightly superior to SFM for detection and characterization of mammographic abnormalities. Despite obvious advantages, the conversion to digital mammography has been slower than anticipated, and not only due to higher costs. Until very recently, some countries did not even permit the use of digital mammography in breast cancer screening. The reason for this reluctant attitude was concern about lower spatial resolution and about using soft-copy reading. Furthermore, there was a lack of data supporting improved diagnostic accuracy using FFDM in a screening setting, since two pioneer trials both showed nonsignificantly lower cancer detection rate at FFDM. The 10 studies comparing FFDM and SFM in mammography screening published so far have shown divergent and rather conflicting results. Nevertheless, there is a rapid conversion to digital mammography in breast cancer screening in many western countries. The aim of this article is to give an updated review of these studies, discuss the conflicting findings, and draw some conclusions from the results.

Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

IntroductionExisting methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.MethodsUsing macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach.ResultsWe identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients.ConclusionThe results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.

Digital breast tomosynthesis (DBT): initial experience in a clinical setting.

Background Digital breast tomosynthesis (DBT) is a promising new technology. Some experimental clinical studies have shown positive results, but the future role and indications of this new technique, whether in a screening or clinical setting, need to be evaluated. Purpose To compare digital mammography and DBT in a side-by-side feature analysis for cancer conspicuity, and to assess whether there is a potential additional value of DBT to standard state-of-the-art conventional imaging work-up with respect to detection of additional malignancies. Material and Methods The study had ethics committee approval. A total of 129 women underwent 2D digital mammography including supplementary cone-down and magnification views and breast ultrasonography if indicated, as well as digital breast tomosynthesis. The indication for conventional imaging in the clinical setting included a palpable lump in 30 (23%), abnormal mammographic screening findings in 54 (42%), and surveillance in 45 (35%) of the women. The women were examined according to present guidelines, including spot-magnification views, ultrasonography, and needle biopsies, if indicated. The DBT examinations were interpreted several weeks after the conventional imaging without knowledge of the conventional imaging findings. In a later session, three radiologists performed a side-by-side feature analysis for cancer conspicuity in a sample of 50 cases. Results State-of-the-art conventional imaging resulted in needle biopsy of 45 breasts, of which 20 lesions were benign and a total of 25 cancers were diagnosed. The remaining 84 women were dismissed with a normal/definitely benign finding and without indication for needle biopsy. The subsequent DBT interpretation found suspicious findings in four of these 84 women, and these four women had to be called back for repeated work-up with knowledge of the tomosynthesis findings. These delayed work-ups resulted in two cancers (increasing the cancer detection by 8%) and two false-positive findings. The side-by-side feature analysis showed higher conspicuity scores for tomosynthesis compared to conventional 2D for cancers presenting as spiculated masses and distortions. Conclusion Tomosynthesis is a promising new technique. Our preliminary clinical experience shows that there is a potential for increasing the sensitivity using this new technique, especially for cancers manifesting as spiculated masses and distortions.

Gene expression profiling of peripheral blood cells for early detection of breast cancer

IntroductionEarly detection of breast cancer is key to successful treatment and patient survival. We have previously reported the potential use of gene expression profiling of peripheral blood cells for early detection of breast cancer. The aim of the present study was to refine these findings using a larger sample size and a commercially available microarray platform.MethodsBlood samples were collected from 121 females referred for diagnostic mammography following an initial suspicious screening mammogram. Diagnostic work-up revealed that 67 of these women had breast cancer while 54 had no malignant disease. Additionally, nine samples from six healthy female controls were included. Gene expression analyses were conducted using high density oligonucleotide microarrays. Partial Least Squares Regression (PLSR) was used for model building while a leave-one-out (LOO) double cross validation approach was used to identify predictors and estimate their prediction efficiency.ResultsA set of 738 probes that discriminated breast cancer and non-breast cancer samples was identified. By cross validation we achieved an estimated prediction accuracy of 79.5% with a sensitivity of 80.6% and a specificity of 78.3%. The genes deregulated in blood of breast cancer patients are related to functional processes such as defense response, translation, and various metabolic processes, such as lipid- and steroid metabolism.ConclusionsWe have identified a gene signature in whole blood that classifies breast cancer patients and healthy women with good accuracy supporting our previous findings.

Breast MRI: EUSOBI recommendations for women's information.

AbstractThis paper summarizes information about breast MRI to be provided to women and referring physicians. After listing contraindications, procedure details are described, stressing the need for correct scheduling and not moving during the examination. The structured report including BI-RADS® categories and further actions after a breast MRI examination are discussed. Breast MRI is a very sensitive modality, significantly improving screening in high-risk women. It also has a role in clinical diagnosis, problem solving, and staging, impacting on patient management. However, it is not a perfect test, and occasionally breast cancers can be missed. Therefore, clinical and other imaging findings (from mammography/ultrasound) should also be considered. Conversely, MRI may detect lesions not visible on other imaging modalities turning out to be benign (false positives). These risks should be discussed with women before a breast MRI is requested/performed. Because breast MRI drawbacks depend upon the indication for the examination, basic information for the most important breast MRI indications is presented. Seventeen notes and five frequently asked questions formulated for use as direct communication to women are provided. The text was reviewed by Europa Donna–The European Breast Cancer Coalition to ensure that it can be easily understood by women undergoing MRI.Key Points• Information on breast MRI concerns advantages/disadvantages and preparation to the examination • Claustrophobia, implantable devices, allergic predisposition, and renal function should be checked • Before menopause, scheduling on day 7–14 of the cycle is preferred • During the examination, it is highly important that the patient keeps still • Availability of prior examinations improves accuracy of breast MRI interpretation

Iterative reconstruction reduces abdominal CT dose.

OBJECTIVE In medical imaging, lowering radiation dose from computed tomography scanning, without reducing diagnostic performance is a desired achievement. Iterative image reconstruction may be one tool to achieve dose reduction. This study reports the diagnostic performance using a blending of 50% statistical iterative reconstruction (ASIR) and filtered back projection reconstruction (FBP) compared to standard FBP image reconstruction at different dose levels for liver phantom examinations. METHODS An anthropomorphic liver phantom was scanned at 250, 185, 155, 140, 120 and 100 mAs, on a 64-slice GE Lightspeed VCT scanner. All scans were reconstructed with ASIR and FBP. Four readers evaluated independently on a 5-point scale 21 images, each containing 32 test sectors. In total 672 areas were assessed. ROC analysis was used to evaluate the differences. RESULTS There was a difference in AUC between the 250 mAs FBP images and the 120 and 100 mAs FBP images. ASIR reconstruction gave a significantly higher diagnostic performance compared to standard reconstruction at 100 mAs. CONCLUSION A blending of 50-90% ASIR and FBP may improve image quality of low dose CT examinations of the liver, and thus give a potential for reducing radiation dose.

Interobserver variation in the interpretation of breast imaging comparison of mammography, ultrasonography, and both combined in the interpretation of palpable noncalcified breast masses

Purpose: To analyze interobserver agreement in the interpretation of palpable noncalcified breast masses by means of mammography, ultrasonography, and a combination of both methods. Material and Methods: Mammograms and ultrasonograms of 100 benign breast masses and 100 malignant ones in 200 patients were retrospectively analyzed by 4 radiologists with experience in both imaging modalities. The images were analyzed independently and without knowledge of the final diagnosis. The analysis was performed in 3 sessions and used a 5-point rating scale for probability of malignancy. The interobserver variation was analyzed by means of observed agreement, kappa, and weighted kappa statistics based on the 5-point rating scale and a 3-level scale of the collapsed 5-point scale. The chi-square statistic was used for testing the equality of the kappa values. Results: The overall kappa value on the 3-level scale was 0.48 (range 0.37-0.61) for ultrasonography, 0.58 (range 0.52-0.66) for mammography, and 0.71 (range 0.63-0.79) for the combined reading. The kappa values were statistically different for ultrasonography but did not differ significantly for the mammographic and combined readings. The combined reading showed higher kappa values than mammography alone, and the improvement was statistically significant for 3 of the 6 pairs of comparison. Conclusion: Radiologists differ substantially in their interpretations of mammograms and breast ultrasonograms. Agreement was highest in the combined reading, intermediate in mammography, and lowest in ultrasonography.

Ultrasonographic evaluation of invasive lobular carcinoma.

Purpose: To compare ultrasonographic (US) and mammographic findings and tumor size measurements of invasive lobular carcinoma (ILC). Material and Methods: US diagnoses and mammographic findings were compared in 95 patients with pure ILC, including 46 palpable and 49 nonpalpable tumors. The diameters of tumors measured by mammography, US, and pathology were compared in 70 of the 95 patients using scatter plots and correlation analysis. Results: Eighty-two (86.3%) of the ILCs were correctly diagnosed as malignant tumor, 5 (5.3%) were diagnosed as focal abnormality, and only 2 patients had normal findings on US. The most common mammographic findings were a spiculated mass (57%) and a focal asymmetric density (15%). US correctly diagnosed 8 of 12 patients with normal or equivocal mammographic findings. The correlation of tumor size assessment on imaging and pathology revealed that US measurements including the “halo” (r=0.69) was superior to that of mammography (r=0.59). ILCs larger than 30 mm were heavily underestimated by both methods. Conclusion: Malignant tumor was diagnosed on US in most of the patients with ILC. US tumor measurement including the “halo” predicted tumor size most accurately. The correlation between imaging measurements and tumor diameter on histology was lower for ILCs than reported for populations of mixed carcinomas.